Abstract
Clinically useful prodrug activation systems for cancer therapy can be applied in combination with the exogenous activating enzymes, by which masked prodrugs are able to unmask to exert cytotoxic effects on the target tumors. In essence, designing prodrugs not to be degenerated or activated by the endogenous enzymes is needed. Prodrug activation systems are to be delivered to the tumor site by delivery tools, including antibodies, genes, viral vectors and synthetic polymers, directed to the target tumors. Highly selective accumulation of the prodrug activation system at the tumor site is critically important for the efficacy of the prodrug activations. Genetic engineering of antibodies have made it possible to create a bispecific antibody and its derivatives, which are of special value to the functional antibodies with one arm to direct the target tumor tissues, and another to recruit the effector cells or molecules that can effectively kill the tumor cells. The technology has further opened the window for catalytic antibodies as a prodrug activating system. Catalytic antibodies have two distinct advantages over the enzymes: First, they can be selected to catalyze the reaction that is not catalyzed by the endogenous enzymes. Second, in order to minimize immunogenicity, humanization is applicable to catalytic antibodies. In viewing the concept and experimental data with a few clinical trials of recent approaches of prodrug activation systems, their potential utility in clinical oncology is further discussed.
Keywords: antibody-directed enzyme, prodrug activation, antibody-directed abzyme prodrug therapy, gene-directed enzyme prodrug therapy, virus-directed enzyme, prodrug therapy, polymer-directed enzyme
Current Pharmaceutical Design
Title: Enzyme / Abzyme Prodrug Activation Systems: Potential Use in Clinical Oncology
Volume: 9 Issue: 26
Author(s): Yoshisuke Nishi
Affiliation:
Keywords: antibody-directed enzyme, prodrug activation, antibody-directed abzyme prodrug therapy, gene-directed enzyme prodrug therapy, virus-directed enzyme, prodrug therapy, polymer-directed enzyme
Abstract: Clinically useful prodrug activation systems for cancer therapy can be applied in combination with the exogenous activating enzymes, by which masked prodrugs are able to unmask to exert cytotoxic effects on the target tumors. In essence, designing prodrugs not to be degenerated or activated by the endogenous enzymes is needed. Prodrug activation systems are to be delivered to the tumor site by delivery tools, including antibodies, genes, viral vectors and synthetic polymers, directed to the target tumors. Highly selective accumulation of the prodrug activation system at the tumor site is critically important for the efficacy of the prodrug activations. Genetic engineering of antibodies have made it possible to create a bispecific antibody and its derivatives, which are of special value to the functional antibodies with one arm to direct the target tumor tissues, and another to recruit the effector cells or molecules that can effectively kill the tumor cells. The technology has further opened the window for catalytic antibodies as a prodrug activating system. Catalytic antibodies have two distinct advantages over the enzymes: First, they can be selected to catalyze the reaction that is not catalyzed by the endogenous enzymes. Second, in order to minimize immunogenicity, humanization is applicable to catalytic antibodies. In viewing the concept and experimental data with a few clinical trials of recent approaches of prodrug activation systems, their potential utility in clinical oncology is further discussed.
Export Options
About this article
Cite this article as:
Nishi Yoshisuke, Enzyme / Abzyme Prodrug Activation Systems: Potential Use in Clinical Oncology, Current Pharmaceutical Design 2003; 9 (26) . https://dx.doi.org/10.2174/1381612033454063
DOI https://dx.doi.org/10.2174/1381612033454063 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Anti-VEGF Mediated Immunomodulatory Role of Phytochemicals: Scientific Exposition for Plausible HCC Treatment
Current Drug Targets HSV-1 Viral Oncolysis and Molecular Imaging with PET
Current Cancer Drug Targets Reactive Oxygen Species in Cancer Biology and Anticancer Therapy
Current Medicinal Chemistry Organophosphorus Chemistry: Therapeutic Intervention in Mechanisms of Viral and Cellular Replication
Current Organic Chemistry Organoselenium Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry Surgical Staging for Cervical Cancer
Current Women`s Health Reviews Crystallization and X-Ray Data Analysis of the Extended Dna-Binding Domain of the E2 Bovine Papillomavirus Type 1 Protein
Protein & Peptide Letters The Therapeutic Potential of Microencapsulate Implants: Patents and Clinical Trials
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Cytokines and Hormones in the Regulation of Hypoxia Inducible Factor-1α (HIF-1α)
Cardiovascular & Hematological Agents in Medicinal Chemistry Amygdalin Decreases Adhesion and Migration of MDA-MB-231 and MCF-7 Breast Cancer Cell Lines
Current Molecular Pharmacology Effect of Curcumin on Pro-angiogenic Factors in the Xenograft Model of Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells
Current Medicinal Chemistry Positron Emission Tomography Imaging of Tumor Hypoxia
Current Medical Imaging A Role for Milk Proteins and their Peptides in Cancer Prevention
Current Pharmaceutical Design Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Defining the Role of Integrin αvβ6 in Cancer
Current Drug Targets α(N)-Heterocyclic Thiosemicarbazones: Iron Chelators that are Promising for Revival of Gallium in Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Advances of Inorganic Materials in the Detection and Therapeutic Uses against Coronaviruses
Current Medicinal Chemistry Application of Mesenchymal Stem Cells in the Targeted Gene Therapy for Gastric Cancer
Current Stem Cell Research & Therapy Magnetic Hyperthermia with Magnetic Nanoparticles: A Status Review
Current Topics in Medicinal Chemistry